Delirium occurs in up to 50% of intensive care unit (ICU) and is associated with substantial mortality and morbidity. Patients who do not meet all of the DSM-IV criteria for delirium are deemed to have subsyndromal delirium. Recent data suggests that subsyndromal delirium occurs in up to 70% of ICU patients (even in patients who do not progress to delirium and increases patient mortality, ICU length of stay and the need for supportive care after ICU discharge. Moreover, recent non-ICU studies demonstrate that low-dose antipsychotic therapy in patients at high risk for delirium improves patient outcome. Preliminary observational data from our research group suggest that ICU patients with subsyndromal delirium who are exposed to haloperidol are more likely to remain in subsydromal delirium and not progress to delirium. We therefore hypothesize that treatment of subsyndromal delirium in the critically ill with low-dose haloperidol will prevent progression to delirium without leading to unwanted adverse effects. The study sample will consist of 68 mechanically ventilated adult medical ICU patients with subsyndromal delirium who do not have underlying conditions that could affect the ability to diagnosis delirium. Participants will be randomly assigned to receive to receive haloperidol 1mg IV every 6 hours or a matching placebo until they are either discharged from the ICU or develop delirium based on evaluation by a psychiatrist. The aims of the study are to assess the impact of haloperidol administration therapy on progression to delirium and patient safety. We will also evaluate the impact of the intervention on patient agitation, duration of mechanical ventilation and post-ICU cognitive function. If haloperidol is found to be safe and effective in the proposed study, larger studies will be needed to determine the effect of haloperidol therapy on patient mortality and evaluate predictors for drug response. Information from the proposed study is greatly needed to determine if there is a safe and effective pharmacological intervention for the estimated 3.5 million Americans each year who develop subsyndromal delirium in the ICU. PUBLIC HEALTH RELEVANCE: Delirium occurs in up to 50% of mechanically ventilated patients admitted to the intensive care unit (ICU). It is associated with higher mortality, longer duration of ICU stay and greater healthcare costs. Moreover, the cognitive dysfunction associated with delirium may persist long after recovery and impact long-term functional ability and quality of life. Given that more than 5 million patients are admitted each year to an ICU in the United States, delirium in the critically ill is a major health care issue. Patients who do not meet all of the DSM-IV criteria for delirium are deemed to have subsyndromal delirium. Subsyndromal delirium, occurring in up to 70% of ICU patients, increases patient mortality and the need for supportive care after ICU discharge [(although not as much as delirium)] [even if it does not transition to delirium]. Given that up 3.5 million Americans may develop subsyndromal delirium each year, an intervention that is found to be safe and effective, particularly if it is of low cost, will have a profound impact on the U.S. healthcare system.